It is very much intriguing to understand and explore how a eukaryotic cell uses a set of rules in distributing various macromolecules to their target destination in a temporally regulated fashion. A large set of molecular machineries function under stringent spatial and temporal regulation to safeguard these rules. Sometimes, these rules are violated which results into pathophysiological situations.
Theme 1
Metastasis is the major cause of high morbidity rates in Cancer. A series of events take place, leading to the dissemination of the tumor growing in a confined area to metastasize and spread to multiple organs resulting in multi-organ failure. Once cancer reaches the invasive stage, the disease becomes much more challenging to treat and life-threatening. Breast cancer is among invasive tumors that show metastasis in the lymph node, lung, brain, and liver. Cancer invasion is attained by the degradation of extracellular matrix (ECM) components and breaching the basement membrane accomplished by the actin rich membrane protrusions called invadopodia. Matrix metalloproteases (MMP) are reported to have a broad range of enzymatic activity towards ECM components and are enriched at invadopodia. Various factors trigger the formation of invadopodia and growth factor receptors are one of them. Growth factor signaling also modulates the expression and activity of various proteases. Currently, we are investigating how the growth factor receptor and membrane-type metalloprotease collectively could promote invadopodia formation and invasion.
Paper-1 Syntaxin7 contributes to breast cancer cell invasion by promoting invadopodia formation
Paper-2 SNX27-retromer Assembly Recycles MT1-MMP to Invadopodia and Promotes Breast Cancer Metastasis
Theme-II
Collective cell migration (CCM) is the process that permits groups of cells to move together in a coordinated manner while remaining connected to each other by cell-cell contacts. Various multicellular organisms rely on CCM which serves as the basis for a plethora of processes ranging from organ development to cancer metastasis. It is a unique mechanism of tumour cell metastasis that differs from typical single tumour cell metastasis in that it does not require a full EMT programme and can travel as a group entity in which cells retain cell-cell connection and exhibit a myriad of epithelial characteristics. Several cancer types have shown evidence of these tumour clusters in the patients’ blood, and is associated with a poor prognosis. Colorectal cancer (CRC) is the fourth most prevalent cause of cancer-related fatalities. 32% of patients with metastatic CRC have detectable one or more tumour clusters per blood draw.But it is unclear what drives the collective behaviour of these CRC tumour clusters. We previously reported that the colonic epithelium-enriched protein PLP2. associates with the tight-junction protein ZO1 and promotes CCM in human colorectal cancer cell line that have undergone partial EMT. The lab is primary focus is to explore the molecular and cellular mechanisms underlying the collective behaviour of the colorectal adenocarcinomas.
Paper-1 PLP2 drives collective cell migration via ZO-1-mediated cytoskeletal remodeling at the leading edge in human colorectal cancer cells.
Theme-III
The pathogenic amoeba, E. histolytca is one of the causatve agents for health hazard in tropical countries. It causes amoebic dysentery, liver abscess in human. About 50 million cases of amebiasis and 40-100 thousand cases of deaths are reported annually. Even though inexpensive treatment is readily available for amebiasis the frequent recurrence occurs because of lack of proper preventive knowledge and poor sanitary system. This makes amebiasis one of the major burdens on the health systems in developing countries. Previous work in the lab has highlighted the function and importance of several GTPases in pathogenicity. We are currently focusing on trogocytosis, the process of internalizing host cells as fragments by the parasite. Trogocytosis is a relatively unexplored process with a possible role in pathogenesis. Our current aim is to uncover the molecular machinery that drives trogocytosis. Trogocytosis is a recently discovered cellular process in the amoebic trophozoites through which the parasite is believed to invade host intestinal cells.
Paper-1 PI Kinase-EhGEF2-EhRho5 axis contributes to LPA stimulated macropinocytosis in Entamoeba histolytica.
EhRho6-mediated actin degradation in Entamoeba histolytica is associated with compromised pathogenicity.